A common method for identifying the presence of organic or inorganic substances in fluids involves capturing the substances with specially treated magnetically responsive spheres that are designed to attach themselves to a substance of interest. The nature of the spheres allows for magnetic management of the spheres in that such spheres are highly permeable with low magnetic retentivity. Thus, the spheres are responsive to and can be manipulated by magnetic fields, yet when the magnetic fields are removed the particles retain no magnetic properties.
Such spheres, or magnetically responsive particles, are commercially available, among other sources, from Dynal Inc., 45 North Station Plaza, Great Neck, N.Y., in 2.8 and 4.5 micron diameter sizes (hereinafter referred to as "Dynal beads" or "beads"). Dynal beads have been used as magnetically responsive beads for isolating, collecting and assaying diagnostic ligates as described in U.S. Pat. No. 5,158,871 ("the '871 patent").
As disclosed in the '871 patent, a suitable ligand is bound to a sheath of an organic substance surrounding the metal oxide core of the magnetically responsive beads. The suitable ligand is capable of binding with a ligate or target substance that is sought to be isolated and is diagnostic of a particular disease state. The ligand/beads are admixed with a fluid containing the ligate sought, for a selected time period and in a manner sufficient to effect a strong attachment between the ligate and ligand/beads to form ligate/ligand/bead complexes.
A magnetic gathering or harvesting device is contemplated in the '871 patent, to attract and retain the complexes in a localized magnetic field for removal from the fluid. The '871 patent suggests only application specific, manually manipulated harvesting devices each suitable for a particular application.
Other known procedures for magnetically managing such beads or other magnetically responsive spheres, typically involve insertion of the magnetically responsive spheres into a fluid to be tested after the spheres have been treated with the appropriate bonding agent for the test. The spheres are admixed in the fluid by shaking, stirring, or pumping to allow for the spheres to come into contact with the target substance. After the complexing phase is complete, i.e., the target substance has been sufficiently exposed to the magnetically responsive spheres with associated bonding agent within the fluid to form sphere/bonding agent/target substance complexes, the complexes including the spheres are removed from the fluid by attracting them toward a particular location with a magnet. Typically, bead concentration is much greater than target substance concentration. Thus, a large number of beads remain free of target substance and some portion of the bead population is bound with target substance.
The non-homogeneous population of target substance bound and unbound spheres is drawn in bulk toward and concentrated in the vicinity of a controller magnet. Manual processing for the separation of the spheres can take many hours and is labor intensive. Only after considerable manual processing can spheres be separated from different populations for microscopic slide preparation. The spheres can then be tested to determine the presence of target substances attached to the surfaces of the spheres. To enhance the capture process, large numbers of spheres are often used. In addition, spheres of different sizes, each treated for a different target substance, may be used. In these cases, it is necessary and desirable, yet difficult, time consuming, labor intensive and costly, to separate spheres from different populations into homogeneous populations for further analysis.